Largest ever Alzheimer's genome study unveils dementia mysteries
07 September 2009
Scientists at the Institute of Psychiatry have been involved with a study that has discovered two new genes associated with Alzheimer’s disease. The results, from the largest ever Alzheimer’s disease genome-wide association study (GWAS) involving 16,000 individuals, are published in Nature Genetics.
The study was funded by the Wellcome Trust, Medical Research Council, Alzheimer’s Research Trust and Welsh Assembly Government among others. The King’s scientists worked with universities in Cardiff, London, Cambridge, Nottingham, Southampton, Manchester, Oxford, Bristol and Belfast, who collaborated with Irish, German, Belgian, Greek and American institutions.
Simon Lovestone, Professor of Old Age Psychiatry at the Institute of Psychiatry, who led the research at King’s along with Dr John Powell, Dr Petra Proitsi and Miss Michelle Lupton comments: ‘This exciting research points the way forward for new understanding of Alzheimer’s disease and is the culmination of over a decade of collaboration between many groups around the world’.
Gene discovery
Previously only one gene, APOE4, had been shown to be a risk factor for Alzheimer’s disease. This study reveals two further genes, CLU and PICALM, are related to Alzheimer’s disease.
Professor Julie Williams, Chief Scientific Adviser to the Alzheimer’s Research Trust, said: ‘Both CLU and PICALM highlight new pathways that lead to Alzheimer's disease. The CLU gene produces clusterin which normally acts to protect the brain in a variety of ways. Variation in this gene could remove this protection and contribute to Alzheimer's development.
‘PICALM is important at synapses - connections between brain cells - and is involved in the transport of molecules into and inside of nerve cells, helping form memories and other brain functions. We know that the health of synapses is closely related to memory performance in Alzheimer's disease, thus changes in genes which affect synapses are likely to have a direct effect on disease development.’
Rebecca Wood, Chief Executive of the Alzheimer’s Research Trust, which part-funded the study, said: ‘These findings are a leap forward for dementia research. At a time when we are yet to find ways of halting this devastating condition, this development is likely to spark off numerous new ideas, collaborations and more in the race for a cure.
The team have shared their data with another GWAS, also published in Nature Genetics, which has revealed compelling evidence for a third gene associated with Alzheimer’s called CR1.
The only other genes that have been connected to Alzheimer’s disease are in extremely rare cases of familial Alzheimer’s disease, which is inherited in less than 1% of cases.
The research shows that other genes can be identified using this method, and the group are already planning a larger study involving 60,000 people, which can be achieved within the next year.
Dr John Powell concludes: ‘The research demonstrates that study of the genes and their identified genetic variants will unravel disease mechanisms and lead to new and improved treatment.’
The October issue of Nature Genetics can be accessed here: http://www.nature.com/ng/journal/v41/n10/index.html